Generally, when a drug is present in various forms including a non-crystalline form, one or more kinds of crystalline form etc., it is obvious in the art that pharmaceutically important factors such as solubility, release characteristics, and bioavailability may vary among their forms. Particularly, in a compound where optical isomers can be present, each isomer may exhibit differences not only in physicochemical properties but also in pharmacological activities and toxicities. Therefore, it is very important to manufacture and/or separate an optical isomer having high pharmacological activity and low toxicity with high-purity. Specifically, regarding polymorphic crystalline forms, if multiple types of crystalline forms are mixed upon completion of the entire formulation procedure due to the occurrence of changes in polymorphic crystalline forms, it may lead to a change in the pharmaceutical properties of the final drug and thereby induce unexpected pharmacokinetic responses. Accordingly, it is very important to obtain a compound in a pure, single crystalline form in order to secure reproducibility of the drug.
Furthermore, in selecting from various crystalline forms, or between a crystalline form and a non-crystalline form, the non-crystalline form has advantages of increasing pharmaceutical efficacy and exhibiting fast action due to its high solubility in general. However, the non-crystalline form has disadvantages of a short shelf-life and difficulty in adjusting the release speed and blood concentration of the drug due to instability. In contrast, the crystalline form, although it has low solubility and thus has a low bioavailability per unit weight, also has advantages in that it can secure stability and prepare formulations capable of long-acting release. As such, because the crystalline form has higher stability and lower solubility than the non-crystalline form, it is necessary to sacrifice solubility when stability is given top priority, whereas stability may be sacrificed when solubility should be considered first, thus making the decision on how to meet both stability and solubility is difficult.